1. Field of the Invention
The present invention is directed to a method of treating a fungal infection, such as athlete's foot, by orally or topically administrating an antiviral agent, such as valacyclovir hydrochloride, acyclovir and famcyclovir to patients suffering from such fungal infection.
2. Description of the Related Art
Athlete's foot is a skin disease, usually occurring between the toes, which is believed currently caused by a fungus. The fungus most commonly attacks the feet because shoes create a warm, dark, and humid environment which encourages fungus growth. The warmth and dampness of areas around swimming pools, showers, and locker rooms, are also breeding grounds for fungi. Because the infection was common among athletes who used these facilities frequently, the term “athlete's foot” became popular. Not all fungus conditions are athlete's foot. Other conditions, such as disturbances of the sweat mechanism, reaction to dyes or adhesives in shoes, eczema, and psoriasis, also may mimic athlete's foot.
The signs of athlete's foot, singly or combined, are itching scaling skin, often accompanied by inflammation, by blisters. Blisters often lead to cracking of the skin. When blisters break, small raw areas of tissue may be exposed, possibly causing pain and swelling. Itching and burning may increase as the infection spreads.
Athlete's foot may invade to the soles of the feet in between the toes and the toenails. It can also be spread to other parts of the body, notably the groin and underarms, by those who scratch the infection and then touch themselves elsewhere. The organisms causing athlete's foot may persist for long periods.
Fungal infection of toenails is a common foot health problem. A majority of victims do not seek treatment or may not even recognize the existence of a problem. Probably because the infection can be present for years without ever causing pain. Its prevalence rises sharply among older adults. Studies estimate that it afflicts three to five percent of the population. However, doctors of podiatric medicine believe that because so many cases go unreported, the incidence may be four times higher than what have been reported. They estimate that about 10 million people are infected annually.
Fungi are simple parasitic plant organisms, such as molds and mildew, that lack chlorophyll and therefore do not require sunlight for growth. A group of fungi called dermatophytes easily attack the nail, thriving off keratin, the nail's protein substance. Fungal infection of the nails is known to Physicians and other physicians as onychomycosis. It is an infection underneath the surface of the nail, which can also penetrate the nail. Onychomycosis is caused by various types of fungi, which are commonly found throughout the environment.
When the tiny organisms take hold, the nail may become thicker, yellowish-brown or darker in color, and foul smelling. Debris may collect beneath the nail plate, white marks frequently appear on the nail plate, and the infection is capable of spreading to other toenails, the skin, or even the fingernails.
Because it is difficult to avoid contact with microscopic organisms like fungi, the toenails are especially vulnerable around damp areas where people are likely to be walking barefoot—swimming pools, locker rooms, and showers, for example. Injury to the nail bed may make it more susceptible to all types of infection, including fungal infection. Those who suffer chronic diseases, such as diabetes, circulatory problems, or immune-deficiency conditions, are especially prone to fungal nails. Other contributory factors may be a history of athlete's foot and excessive perspiration.
The disease, characterized by a change in a toenail's color, is often considered nothing more than a mere blemish—ugly and embarrassing. In many cases, however, that change in color is the start of an aggravating disease that ultimately could take months to control. If it is ignored, its spread could impair one's ability to work or even walk. That happens because it is frequently accompanied by thickening of the nails, which then cannot easily be trimmed and may cause pain while wearing shoes. This disease can frequently be accompanied by a secondary bacterial and/or yeast infection in or about the nail plate.
It is not easy to prevent athlete's foot because it is usually contracted in dressing rooms, showers, and swimming pool locker rooms where bare feet come in contact with the fungus. Fungicidal and fungistatic chemicals, used for athlete's foot treatment, frequently fail to contact the fungi in the horny layers of the skin.
Physicians can detect a fungal infection early, culture the nail, determine the cause, and form a suitable treatment plan, which may include prescribing topical or oral medication, and debridement (removal of diseased nail matter and debris) of an infected nail. Indeed, debridement is one of the most common foot care procedures performed by DPMs.
If a Physician determines a fungus is the cause of the problem, a specific treatment plan, including the prescription of antifungal medication, applied topically or taken by mouth, will usually be suggested. If there is a secondary infection caused by bacteria, antibiotics, such as penicillin, may be prescribed. Depending on the nature of the infection and the severity of each case, treatment may vary.
However, even the best counter treatments may not prevent a fungal infection from coming back. A fungus may work its way through the entire nail, penetrating both the nail plate and the nail bed. If an infection is not overcome, or continues to reappear, further medical attention will be necessary.
Newer oral antifungals such as lamisil approved by the Food and Drug Administration such as lausid spervenoy, may be the most effective treatment. They offer a shorter treatment outlook (three to four months) and improved effectiveness, though physicians advise that lengthier treatments, up to 12 months, may still be required for some infections. Current studies show that, for a small percentage of the population, there are some unwanted side effects caused by any oral antifungal.
The commercially available anti-viral agents, such as acyclovir, valacyclovir, famciclovir, and ganciclovir, combat against human herpes virus mainly by inhibiting viral replication. Acyclovir has proven to be specifically effective against herpes simplex (HSV) 1 and 2 and herpes zoster. Acyclovir is a guanosine analog with an acyclic side chain at the 9 position. Acyclovir selectively acts against human herpes viruses, including HSV-1/-2, varicella zoster virus (VZV), Epstein-Barr virus (EBV) and cytomegalovirus (CMV) through several enzymatic reactions, each of which is unique to virus replication: specific activation (phosphorylation) by a virus-induced thymidine kinase (TK); selective inhibition of the viral DNA polymerase by acyclovir di- and triphosphate (ACVTP) acting as a competitor with the natural substrate, dGTP; termination of viral DNA chain growth by incorporation of acyclovir monophosphate (ACVMP); and inactivation of the viral DNA polymerase following ACVMP incorporation in the presence of dNTPs. More specifically, acyclovir is transported into cells by the nucleoside transporter which also transports guanine. It requires a virus-encoded TK for efficient intracellular activation which accounts, in part, for its selectivity.
Valacyclovir, valine ester of acyclovir, is one of a number of oral acyclocvir prodrugs which lead to higher blood levels than the parent compound. Valacyclovir turns into acyclovir in the patient's body after administration. It functions against human herpes viruses through the same mechanism as acyclovir.
Valacyclovir hydrochloride (tradename Valtrex) is the hydrochloride salt of L-valyl ester of acyclovir. The chemical name of valacyclovir hydrochloride is L-valine, 2-[(2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy]ethyl ester, monhydrochloride. After oral administration, valacyclovir is rapidly and almost completely converted to acyclovir and L-valine, a naturally occurring amino acid.
Famciclovir, a prodrug of penciclovir, is related to acyclovir but its activated triphosphate form has a much lower intracellular half-life than ACVTP. Penciclovir triphosphate has a hydroxy group at a position corresponding to the 3′ hydroxyl of the 2,-deoxyribose ring, although it is not an obligate chain-terminator, it inhibits DNA polymerization and virus replication. Since penciclovir itself has poor oral bioavailability, famciclovir was developed which is a diester prodrug with good absorption properties.
Ganciclovir is an acyclic nucleoside analogue of 2′-deoxyguanosine that inhibits replication of herpes viruses. Ganciclovir triphosphate is believed to inhibit viral DNA synthesis by (1) competitive inhibition of viral DNA polymerases; and (2) incorporation into viral DNA, resulting in eventual termination of viral DNA elongation.
Penciclovir is known as 9-[4-hydroxy-3-(hydroxymethyl)butyl]guanine. It has inhibitory activity against herpes simplex virus types 1 (HSV 1) and 2 (HSV 2). In vitro studies demonstrate that penciclovir triphosphate inhibits HSV polymerase competitively with deoxyguanosine triphosphate. Consequently, herpes viral DNA synthesis and, therefore, replication are selectively inhibited. In cell culture, penciclovir exhibits antiviral activity against HSV-1 and HSV-2.
Insofar as applicants know, the above described antiviral drugs have never been used to treat athlete's foot or any fungus infections.